Divesiran Eliminates Need for Phlebotomy in 88% of Patients With Polycythemia Vera

Divesiran, an investigational siRNA therapy, resulted in a treatment response in 88% of patients with polycythemia vera, compared with 19% of patients who received placebo, according to topline results from the phase 2 SANRECO trial. The primary end point defined a response as maintaining a hematocrit below 45% between weeks 18 and 36 without requiring phlebotomy, the removal of blood to lower red blood cell levels.

Divesiran works by silencing the TMPRSS6 gene, which increases levels of hepcidin, a hormone that regulates iron availability. By reducing the amount of iron available to the bone marrow, the treatment aims to limit the excessive production of red blood cells associated with polycythemia vera, which is what pushes hematocrit (the share of blood made up of red blood cells) above normal levels.

"Across the SANRECO phase 1/2 program, divesiran has been well tolerated and has consistently delivered durable hematocrit control in phlebotomy-dependent patients with [polycythemia vera], regardless of risk level or disease severity," said Dr. Marina Kremyanskaya in a press release issued by Silence Therapeutics.

What did topline results from the phase 2 SANRECO trial show?

Both dose groups had response rates of 93.8% and 81.3% for the every-six-weeks and every-12-weeks schedules, respectively. The difference between the divesiran and placebo groups was statistically significant.

The trial also met a key secondary end point measuring how often patients needed phlebotomy over weeks 0 to 36. Patients treated with divesiran averaged 0.2 phlebotomies each, compared with 2.1 for those who received placebo and continued to rely on phlebotomy for hematocrit control. Patients who received divesiran also showed improvement in hematocrit control, iron markers including ferritin, and patient-reported symptoms.

What did the phase 2 SANRECO trial evaluate?

The phase 2 portion of SANRECO is an ongoing, three-part, global, randomized, double-blind, placebo-controlled study in 48 patients. Patients were randomly assigned to receive divesiran 6 milligrams per kilogram as an injection under the skin either every six weeks or every 12 weeks, or placebo, for 36 weeks.

All patients still had uncontrolled hematocrit and still required phlebotomy despite standard treatment, which could include hydroxyurea, interferon and/or ruxolitinib. Everyone in the trial has finished the placebo-controlled portion and has moved into three-year double-blind and open-label extension periods.

What are the side effects associated with divesiran?

Divesiran was well tolerated, and safety was consistent with previous trials, with no new safety findings. Injection site reactions were infrequent and self-limiting. Investigators reported two cases of grade 1(mild) anemia, a low red blood cell count.

Silence Therapeutics plans to present full phase 2 results at a future medical conference and expects to begin a phase 3 trial comparing divesiran given every 12 weeks with placebo in the first half of 2027.

References

1. 1. News release. "Silence Therapeutics Announces Positive Topline Results from Phase 2 SANRECO Trial of Divesiran in Polycythemia Vera, Supporting its Potential Best-in-Class Profile." Silence Therapeutics plc. Posted: August 10, 2026.

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